Evaluation on Hepatoprotection of Dihydromyricetin in Acetaminophen-Induced Hepatotoxicity Based on Analysis of Inflammation and Apoptosis Mediated by PI3K/AKT Pathway

Abstract

Purpose: We aimed to investigate whether dihydromyricetin (DHM) could alleviate acetaminophen (APAP)-induced liver damage in mice, and to verify whether the process is associated with the PI3K/AKT signaling pathway. Methods: The contents of DHM in serum and related physiological indicators in blood and liver tissue were measured, respectively. We used haematoxylin and eosin (H&E), TUNEL, Hoechst 33,258, immunofluorescence assay and western blot methods to comprehensively assess the protective mechanism and therapeutic effect of DHM on liver damage induced by APAP (250 mg/kg) in mice. Results: APAP (250 mg/kg) could increase the expression of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β) and cause 4-hydroxy-2-nonenal (4-HNE) and Cytochrome P450 2E1 (CYP2E1) overexpression and stress response in the PI3K/AKT pathway. DHM was also detected in the serum of mice about five minutes after administration. DHM pretreatment could reverse GSH depletion and CYP2E1 overexpression, reduce the expression of ALT, AST, malondialdehyde, 4-HNE, TNF-α, and IL-1β, meanwhile it could reverse the abnormal expression of PI3K/AKT signaling pathway-related proteins which were induced by APAP. DHM pretreatment significantly reduced APAP-induced liver tissue apoptosis, necrosis, and inflammatory infiltration. Conclusion: DHM had a hepatoprotective effect on hepatotoxicity induced by APAP, which was shown by inhibiting oxidative stress and inflammatory responses, and reducing hepatocyte apoptosis by activating the PI3K/AKT signaling pathway.